MECHANISMS OF ANGIOTENSIN-INDUCED HYPOTENSION AND BRADYCARDIA IN THE MEDIAL SOLITARY TRACT NUCLEUS

The selective angiotensin (ANG) II antagonists losartan (AT(1)) and CGP-42112A (AT(2)) were used to determine the receptor subtype and neuronal pathways that mediate the hypotension and bradycardia produced by 200 fmol of ANG II microinjected into the dorsal medial nucleus tractus solitarii (NTS) or dorsal motor nucleus of the vagus (dmnX) in anesthetized rats. At dorsal medial NTS sites (0.3 mm below the surface) where L-glutamate microinjections produced maximal decreases in mean arterial pressure (MAP) and heart rate (HR), ANG II (200 fmol, 50 nl, n = 16) elicited hypotension (-22 +/- 1 mmHg) and bradycardia (-26 +/- 2 beats/min). Although L-glutamate also suppressed respiration, ANG II injections in the medial NTS did not alter respiration. Losartan injected at the medial NTS site caused a dose-dependent reduction of ANG II-induced decreases in MAP and HR. At 2 pmol, the AT(1) antagonist attenuated the responses to ANG II, whereas 100 pmol abolished the effects of ANG II microinjections. In contrast, the AT(2) antagonist CGP-42112A (100 pmol) had no effect on the responses to ANG II. Neither ANG II antagonist altered the cardiovascular effects of L-glutamate injections. Losartan injected into the dmnX blocked hypotension and bradycardia produced by ANG II at that site but did not prevent responses to subsequent ANG II injections in the medial NTS. These observations reveal that the bradycardia and hypotension evoked by ANG II in the dorsal medulla are mediated by the AT(1)-receptor subtype and establish that the cardioinhibitory effects of ANG II in the dorsal medial NTS are mediated by neuronal mechanisms originating within the NTS rather than by diffusion of the peptide into the underlying dmnX.